Ketamine Meets ‘Gold Standard’ in Major Depression Trial

SAN FRANCISCO — Ketamine is as effective as electroconvulsive therapy (ECT) in improving treatment-resistant major depression in outpatients without psychotic features, according to the ELEKT-D randomized trial.

After the 3-week treatment period, 55.4% of patients in the ketamine group and 41.2% of patients in the ECT group responded to treatment, a difference of 14.2% (95% CI 3.9-24.2), within the non-inferiority range of the trial Fits well inside. threshold (P.<0.001), reported Dr. Amit Anand of Brigham and Women's Hospital in Boston and colleagues.

Response was defined as a ≥50% reduction from baseline in the score of the 16-item Quick Self-Report of Depressive Symptoms Inventory (QIDS-SR-16).

The results were announced at the following ceremony. American Psychiatric Association (APA) Issued at the same time as the Annual General Meeting New England Journal of Medicine.

“It’s surprising that ketamine isn’t recessive, because ECT has been the gold standard for treating resistant depression for 80 years,” Anand said. Today’s Medpage. “And indeed, the efficacy of ketamine for major depression without psychotic features appears to be slightly superior to ECT in overall outcomes.”

“But our initial hypothesis and research plan was to test whether ketamine is non-inferior to ECT,” explained Anand. “Therefore, this paper cannot comment on the superiority of ketamine compared to ECT in the treatment of nonpsychotic-resistant depression.”

and Accompanying editorialpointed out Robert Friedman, M.D., Ph.D., of the University of Colorado School of Medicine in Aurora.[i]It is worth noting that all patients considered for participation in the trial were initially referred to ECT because they and their clinicians considered ECT to be the best option. ”

Similar findings were seen when observing treatment response as measured by at least a 50% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) score. This was achieved by 50.8% of his ketamine-treated patients and 41.1% of ECT patients.

Remission of depression (score ≤5), as measured by QIDS-SR-16, was achieved in 32.3% of patients in the ketamine group and 20% in the ECT group. When remission was measured using the MADRS score (score ≤10), 37.9% in the ketamine group and 21.8% in the ECT group achieved remission.

Both treatments significantly improved patient-reported quality of life, which was one of the secondary outcomes of the trial. Measured using a 16-item Quality of Life Scale, there were changes of 12.3 and 12.9 points in the ketamine- and ECT-treated groups, respectively.

At the end of treatment, memory function was lower in the ECT group compared with the ketamine group (difference 1.1 points lower, 95% CI 0.9-1.2). This included a decline from baseline in delayed recall scores in the ECT group. Ketamine-treated patients also reported fewer cognitive symptoms at the end of the treatment phase than did the ECT group.

Ketamine before ECT?

“This study is important for both ECT and ketamine treatment for treatment-resistant depression,” added Anand. “First, we show that ECT in the routine outpatient treatment of resistant depression is not as effective as reported in research studies that are primarily inpatient populations or that do not discriminate. We also show that ketamine is at least as effective, which is effective and could be a treatment option prior to ECT treatment.”

“It also shows that even patients who are resistant to multiple antidepressant treatment trials have about a 50% chance of achieving significant improvement with any one treatment that improves their quality of life,” he said. pointed out.

A total of 25.1% in the ketamine group and 32.4% in the ECT group experienced at least one moderate or severe adverse event during treatment, but no deaths occurred during the study. More ECT patients experienced muscle pain and weakness, and more ketamine-treated patients experienced dissociative symptoms. Four of 200 patients in the ketamine-treated group reported new suicidal ideation, whereas 6 of 203 patients in the ECT group attempted suicide during follow-up.

Participants were selected from one of five testing sites: Baylor College of Medicine in Houston, Johns Hopkins College of Medicine in Baltimore, Cleveland Clinic Lutheran Hospital, Mount Sinai School of Medicine in New York City, and Yale University School of Medicine in New Haven, Connecticut. recruited in one. .

Noting that these are the “major clinical centers” in the United States, Anand said, “In other places where resources are less abundant, ECT may be less rigorously enforced and response rates may be even lower. There is,” he said.

Trial details

This open-label study randomized 403 nonpsychotic treatment-resistant major depression patients to receive either ketamine or ETC. Mean age was 46 years, mean baseline MADRS and QIDS-SR-16 scores were 32 and 18, respectively. A small proportion of both groups had previously received ECT (11.5% in the ketamine group and 10.3% in the ECT group) and had also been treated with ketamine (7% and 3.9%). For the primary endpoint, the statistical design considered a 10% lower response rate in the ketamine group.

During the 3-week treatment phase, ketamine patients received IV treatment twice weekly at a sub-anesthetic dose of 0.5 mg/kg body weight over 40 minutes, with dose modifications as needed. The IV form of ketamine is FDA-approved only as a sedative, analgesic, and general anesthetic. Esketamine (Supravato) Nasal sprays are approved in combination with oral antidepressants for treatment-resistant depression.

ETC patients were recommended to receive 3 weekly sessions designated as right unilateral ultrashort pulses at 6 times the seizure threshold determined at the first visit, but were subsequently modified as needed.

Approximately 93% of both treatment groups completed full treatment. Ketamine dose remained constant in almost all patients, but 39% of ECT patients changed from right unilateral to bilateral therapy.

After the 3-week treatment phase, responding patients were followed for an additional 6 months. During this period, 19.0% in the ketamine group and 35.4% in the ECT group relapsed at month 1, and 34.5% and 56.3%, respectively, relapsed by month 6.

Friedman commented that this six-month follow-up did not last long. Another limitation of the trial is that the researchers did not examine future drug-seeking behavior in ketamine recipients.

“While patients in ECT referral clinics may seem unlikely to be involved in a wave of drug addiction, even in this study, 41% of participants who became addicted , and continued treatment with ketamine.We were assigned to administer ketamine during the first 3-week treatment phase,” he said.

Dr. Friedman suggested that ketamine users should be very aware of the potential downsides of treatment, as side effects such as addiction, dissociation and paranoia increase with longer duration of treatment.

“The next step is to compare the efficacy of ECT and ketamine in other treatment settings and populations where ECT is the only recommended option,” Anand said.

”one [study] “This is depression associated with acute suicidal ideation and suicidal behavior,” he said. to develop laws,” he said.